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Total 198 results found since Jan 2013.
Platelets and von Willebrand factor in atherogenesis
The role of platelet adhesion, activation, and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well established. There is increasing evidence that platelet-endothelial interactions also contribute to early atherosclerotic plaque initiation and growth. Through these interactions, platelet-derived factors can contribute to the proinflammatory and mitogenic status of resident mural cells. Among the many putative mechanisms for platelet-endothelial interactions, increased endothelial-associated von Willebrand factor, particularly in a multimerized form, which interacts with platelet gly...
Source: Blood - March 15, 2017 Category: Hematology Authors: Wu, M. D., Atkinson, T. M., Lindner, J. R. Tags: Hematopoiesis and Stem Cells, Thrombosis and Hemostasis, Vascular Biology, Blood Spotlight Source Type: research
Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutation
We describe here that disruption of FH function on the cell surface can also lead to disseminated complement-dependent macrovascular thrombosis. By gene targeting, we introduced a point mutation (W1206R) into murine FH that impaired its interaction with host cells but did not affect its plasma complement-regulating activity. Homozygous mutant mice carrying this mutation developed renal TMA as well as systemic thrombophilia involving large blood vessels in multiple organs, including liver, lung, spleen, and kidney. Approximately 30% of mutant mice displayed symptoms of stroke and ischemic retinopathy, and 48% died premature...
Source: Blood - March 1, 2017 Category: Hematology Authors: Ueda, Y., Mohammed, I., Song, D., Gullipalli, D., Zhou, L., Sato, S., Wang, Y., Gupta, S., Cheng, Z., Wang, H., Bao, J., Mao, Y., Brass, L., Zheng, X. L., Miwa, T., Palmer, M., Dunaief, J., Song, W.-C. Tags: Immunobiology, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events
Factor XI deficiency is one of the rare inherited coagulation factor deficiencies. However, its incidence is high within the Ashkenazi Jewish community. Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may exist with factor XI deficiency. This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. All adults tested for factor XI activity between 2002 and 2014 were included in the study. Factor XI activity was classified into 3 categories: normal (a...
Source: Blood - March 1, 2017 Category: Hematology Authors: Preis, M., Hirsch, J., Kotler, A., Zoabi, A., Stein, N., Rennert, G., Saliba, W. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism
Recent genome-wide association studies (GWAS) have confirmed known risk mutations for venous thromboembolism (VTE) and identified a number of novel susceptibility loci in adults. Here we present a GWAS in 212 nuclear families with pediatric VTE followed by targeted next-generation sequencing (NGS) to identify causative mutations contributing to the association. Three single nucleotide polymorphisms (SNPs) exceeded the threshold for genome-wide significance as determined by permutation testing using 100 000 bootstrap permutations (P < 10–5). These SNPs reside in a region on chromosome 6q13 comprising the genes smal...
Source: Blood - February 8, 2017 Category: Hematology Authors: Rühle, F., Witten, A., Barysenka, A., Huge, A., Arning, A., Heller, C., Krümpel, A., Mesters, R., Franke, A., Lieb, W., Riemenschneider, M., Hiersche, M., Limperger, V., Nowak-Göttl, U., Stoll, M. Tags: Thrombosis and Hemostasis Source Type: research
How I use anticoagulation in atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia and conveys a significant risk of morbidity and mortality due to related stroke and systemic embolism. Oral anticoagulation (OAC) is the mainstay of thromboembolism prevention, and management of anticoagulation can be challenging. For patients without significant valvular disease, decisions around anticoagulation therapy are first based on the presence of additional stroke risk factors, as measured by the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65–74, and sex c...
Source: Blood - December 21, 2016 Category: Hematology Authors: Steinberg, B. A. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis Source Type: research
How I treat patients with inherited bleeding disorders who need anticoagulant therapy
Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we rev...
Source: Blood - July 13, 2016 Category: Hematology Authors: Martin, K., Key, N. S. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Flanagan JM, Sheehan V, Linder H, et al. Genetic mapping and exome sequencing identify 2 mutations associated with stroke protection in pediatric patients with sickle cell anemia. Blood. 2013;121(16):3237-3245.
Source: Blood - June 15, 2016 Category: Hematology Tags: Free Research Articles ERRATA Source Type: research
Dissecting stroke for anti-VWF therapeutics
Source: Blood - May 11, 2016 Category: Hematology Authors: Dong, J.-f. Tags: Free Research Articles COMMENTS Source Type: research
ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice
Rapid vascular recanalization forms the basis for successful treatment of cerebral ischemia. Currently, tissue plasminogen activator (t-PA) is the only approved thrombolytic drug for ischemic stroke. However, t-PA does not always result in efficient thrombus dissolution and subsequent blood vessel recanalization. To better understand thrombus composition, we analyzed thrombi retrieved from ischemic stroke patients and found a distinct presence of von Willebrand factor (VWF) in various samples. Thrombi contained on average 20.3% ± 10.1% VWF, and this was inversely correlated with thrombus red blood cell content. We h...
Source: Blood - May 11, 2016 Category: Hematology Authors: Denorme, F., Langhauser, F., Desender, L., Vandenbulcke, A., Rottensteiner, H., Plaimauer, B., Francois, O., Andersson, T., Deckmyn, H., Scheiflinger, F., Kleinschnitz, C., Vanhoorelbeke, K., De Meyer, S. F. Tags: Thrombosis and Hemostasis Source Type: research
Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities
We present the long-term follow-up of SCA children from the Créteil newborn cohort (1992-2012) detected at risk by TCD and placed on chronic transfusions. Patients with normalized velocities and no stenosis were treated with hydroxyurea, known to decrease anemia and hemolytic rate. Trimestrial Doppler was performed and transfusions restarted immediately in the case of reversion to abnormal velocities. Patients with a genoidentical donor underwent transplant. Abnormal time-averaged maximum mean velocities (TAMMV) ≥200 cm/s were detected in 92 SCA children at a mean age of 3.7 years (range, 1.3-8.3 years). No strok...
Source: Blood - April 6, 2016 Category: Hematology Authors: Bernaudin, F., Verlhac, S., Arnaud, C., Kamdem, A., Hau, I., Leveille, E., Vasile, M., Kasbi, F., Madhi, F., Fourmaux, C., Biscardi, S., Gluckman, E., Socie, G., Dalle, J.-H., Epaud, R., Pondarre, C. Tags: Pediatric Hematology, Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations Source Type: research
Prothrombotic lipoprotein patterns in stroke
Source: Blood - March 10, 2016 Category: Hematology Authors: Podrez, E. A., Byzova, T. V. Tags: Free Research Articles COMMENTS Source Type: research
Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation
L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher ...
Source: Blood - March 10, 2016 Category: Hematology Authors: Shen, M.-Y., Chen, F.-Y., Hsu, J.-F., Fu, R.-H., Chang, C.-M., Chang, C.-T., Liu, C.-H., Wu, J.-R., Lee, A.-S., Chan, H.-C., Sheu, J.-R., Lin, S.-Z., Shyu, W.-C., Sawamura, T., Chang, K.-C., Hsu, C. Y., Chen, C.-H. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Central nervous system complications and management in sickle cell disease
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ~11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA ...
Source: Blood - February 18, 2016 Category: Hematology Authors: DeBaun, M. R., Kirkham, F. J. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis, Review Articles, Review Series, Clinical Trials and Observations Source Type: research
Low ADAMTS13 activity is associated with an increased risk of ischemic stroke
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) has antithrombotic properties because it cleaves von Willebrand factor (VWF) in smaller, less active multimers. The aim of our study was to investigate prospectively the association between ADAMTS13 activity and ischemic stroke. We included 5941 individuals ≥55 years without a history of stroke or transient ischemic attack (TIA) of the Rotterdam Study, a population-based cohort study. ADAMTS13 activity was measured at inclusion with the FRETS-VWF73 assay and VWF antigen (VWF:Ag) levels by enzyme-linked immunosorbent assay. We assessed ...
Source: Blood - December 17, 2015 Category: Hematology Authors: Sonneveld, M. A. H., de Maat, M. P. M., Portegies, M. L. P., Kavousi, M., Hofman, A., Turecek, P. L., Rottensteiner, H., Scheiflinger, F., Koudstaal, P. J., Ikram, M. A., Leebeek, F. W. G. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Platelet-derived VWF in the stroke spotlight
Source: Blood - October 1, 2015 Category: Hematology Authors: Flood, V. H. Tags: Free Research Articles COMMENTS Source Type: research
